SURA dose reduction may
be necessary. See also Table 4.
Antivirals
Cobicistat
Darunavir (ritonavir-boosted)
Elvitegravir (ritonavir-boosted)
Fosamprenavir (ritonavir-boosted)
Indinavira
Ritonavir
Saquinavir
Monitor for adverse reactions. TOLSURA dose reduction may
be necessary. For, cobicistat, elvitegravir, indinavir, ritonavir,
and saquinavir, see also Table 4.
Calcium Channel Blockers
Diltiazem Monitor for adverse reactions. TOLSURA dose reduction may
be necessary. See also Table 4.
Gastrointestinal Drugs
Drugs that reduce gastric acidity e.g. acid
neutralizing medicines such as aluminum
hydroxide, or acid secretion suppressors such as
H2- receptor antagonists and proton pump
inhibitors (e.g., omeprazole).
Co-administration of these drugs, including omeprazole, with
TOLSURA increases the systemic exposure to itraconazole.
Monitor for adverse reactions. TOLSURA dose reduction may
be necessary [see Clinical Pharmacology (12.3)].
Drug Interactions with Other Drugs that Decrease TOLSURA Concentrations and May Reduce Efficacy of
TOLSURA
Antibacterials
Isoniazid
Rifampicina
Not recommended 2 weeks before and during TOLSURA
treatment.
Rifabutina Not recommended 2 weeks before, during, and 2 weeks after
TOLSURA treatment. See also Table 4.
Concomitant Drug Within Class Prevention or Management
Anticonvulsants
Phenobarbital
Phenytoina
Not recommended 2 weeks before and during TOLSURA
treatment.
Carbamazepine Not recommended 2 weeks before, during, and 2 weeks after
TOLSURA treatment. See also Table 4.
Antivirals
Efavirenza
Nevirapinea
Not recommended 2 weeks before and during TOLSURA
treatment.
Miscellaneous Drugs and Other Substances
Lumacaftor/Ivacaftor Not recommended 2 weeks before, during, and 2 weeks after
TOLSURA treatment.
a Based on clinical drug interaction information with itraconazole.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no data on exposure to itraconazole during pregnancy for the approved indications.
Published epidemiologic studies of women exposed to short courses of treatment withitraconazole in the first trimester of pregnancy have reported no risk of major birth defectsoverall and inconclusive findings on the risk of miscarriage (see Data).
In animal reproduction studies, itraconazole was found to cause a dose-related increase inmaternal toxicity, embryotoxicity, and teratogenicity in rats at dosage levels of approximately (6-25 times the maximum recommended human dose [MRHD] of 390 mg/day based on mg/kgcomparisons), and in mice at dosage levels of approximately 80 mg/kg/day (12 times theMRHD).
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. Theestimated background risk of major birth defects and miscarriage for the indicated populations isunknown. In the U.S. general population, the estimated background risk of major birth defectsand miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Human Data
Published prospective and retrospective cohort studies of women exposed to short courses oftreatment with itraconazole in the first trimester of pregnancy (sample size 198-687) havereported no increase in the rate of major birth defects. The most important methodologicallimitation of th |
